Higher-Dose Vitamin D in Healthy Adults May Harm Bone Health

By Megan Brooks

August 28, 2019

NEW YORK (Reuters Health) - Higher doses of vitamin D in healthy adults who aren't vitamin D deficient do not improve bone health and may actually be harmful, according to a randomized controlled trial.

"For people who fit that description (the majority of Americans and Canadians), the study indicates there is no bone benefit to be obtained by taking doses of vitamin D at or above the tolerable upper intake level (4,000 IU/day)," Dr. David Hanley, professor emeritus at the University of Calgary, who worked on the study, told Reuters Health by email.

"The subjects taking the 400 IU daily dose had a stable, normal level of serum 25-OH vitamin D throughout the study, indicating that dose of supplementation is adequate to maintain whatever bone benefit can be expected from vitamin D in people who are not vitamin D deficient," Dr. Hanley said.

However, the study does "raise the possibility that high-dose vitamin D (4,000 IU/day or higher) has a detrimental effect on bone, but this would require confirmation by another randomized clinical trial," he noted. The study was published online August 27 in JAMA.

The Calgary team assessed the dose-dependent effect of vitamin D supplementation on volumetric bone-mineral density and strength in 311 healthy adults (53 men; mean age, 62) without osteoporosis and with baseline 25-hydroxyvitamin D (25-OHD) levels of 30 to 125 nmol/L. For three years, participants took daily doses of vitamin D3 of 400, 4,000 or 10,000 IU. Calcium supplements were provided to those with dietary intake of less than 1,200 mg/day.

Levels of 25-OHD at baseline, three months and three years were 76.3, 76.7, and 77.4 nmol/L in the 400-IU group; 81.3, 115.3, and 132.2 in the 4,000-IU group; and 78.4, 188.0, and 144.4 in the 10,000-IU group.

Contrary to expectation, at three years, radial volumetric BMD was significantly lower in the 4,000-IU group and the 10,000-IU group, compared with the 400-IU group. The average percent change in volumetric BMD was -2.4% in the 4,000-IU group and -3.5% in the 10,000 IU group versus -1.2% in the 400-IU group.

Tibial volumetric BMD was significantly lower only with the daily dose of 10,000 IU. There were no significant differences in bone strength at either the radius or tibia.

"Further studies would be required to determine if the high doses are harmful, but our results indicate that taking the recommended dose (400 IU plus dietary intake) of vitamin D supplements is the best result for bone health," Dr. Steven Boyd, director of the McCaig Institute for Bone and Joint Health at the University of Calgary, who also worked on the study, told Reuters Health by email.

"The negative effect of a high dose on bone health over three years on bone density did not translate into reduced bone strength, but it would be reasonable to postulate that taking high doses for sustained periods of time beyond three years could negatively affect bone strength," said Dr. Boyd.

Dr. Hanley said, "There is some clinical trial evidence that intermittent very-high-dose vitamin D is associated with increased fracture risk in the elderly (500,000 IU once yearly)." (http://bit.ly/2zpOpCB)

"We did not test doses between 400 and 4,000 IU/day, but based upon other recently published studies and meta-analyses, it appears unlikely those doses would provide improvements in bone density or strength," he added.

Funding for the study was provided by Pure North S'Energy Foundation in response to an investigator-initiated research grant proposal.

SOURCE: http://bit.ly/342sUWz

JAMA 2019.